The goal of the Migration and Metastasis Program is to create an intellectual and scientific environment that facilitates and enhances progress towards understanding the basic processes that underlie metastasis, and design and test strategies for intervention in these processes. Understanding the molecular and cellular basis for metastasis requires defining the changes that cells undergo during cancer progression. This Program focuses on how changes in extracellular matrix, adhesion proteins, adhesion activated signaling pathways and changes in gene expression drive the fundamental steps in metastasis. Research in the Program emphasizes understanding these complex processes in cancer cells/tumors and in the context of normal cell/tissue interactions. The Program is comprised of 18 investigators from 7 Departments. Importantly, 11 of the investigators are new to this Program since the last renewal. The Program has coalesced around two fundamental migration/metastasis-related themes: first, cell-cell and cell-matrix interactions, adhesion signaling and migration/metastasis; and second, the role of extracellular matrix molecules in cell adhesion, cell differentiation and vasculogenesis. The accomplishments of the Program include, understanding Integrin signaling and vasculogenesis, assembly and turnover of cellular adhesions and cell migration, integrin signals and DNA damage, E-cadherin-beta catenin signaling in cancer cells, function of ADAMS proteins, understanding problems of host-tumor microenvironment and numerous authoratative reviews on aspects of migration and metastasis. Because cell migration is so key to the cancer problem, the Program provides intellectual and technical resources to many individuals within the Cancer Center. Program members are experts in cellular imaging, in vivo imaging, use of biosensors for real time imaging, gene array analysis, protein analysis and purification, mechanotransduction, and animal models for cancer. The intellectual vitality of the Program is supported by numerous seminars focusing on problems of cell migration, adhesion, ECM and cell signaling, journal clubs, "research in progress meetings" and membership on student thesis committees. The members of this Program have published 331 papers since the last renewal, of which 5% are intra-programmatic and 20% are inter-programmatic. In the current budget year, the members of this Program are responsible for $480K in direct costs from NCI-funded awards, out of a peer reviewed direct cost funding total of $9.7M. Total NIH funding has increased four-fold since the last renewal. In summary, Program 4-Migration and Metastasis is an exceptional, scientifically active Program whose members make significant contributions to understanding the fundamental processes of cell migration and cancer cell metastasis and significantly contribute to the mission of the CCSG and Cancer Center.